FI950230A - Amino acid-linked nitrogen mustard derivatives and their use as prodrugs in the treatment of tumors - Google Patents

Amino acid-linked nitrogen mustard derivatives and their use as prodrugs in the treatment of tumors Download PDF

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Publication number
FI950230A
FI950230A FI950230A FI950230A FI950230A FI 950230 A FI950230 A FI 950230A FI 950230 A FI950230 A FI 950230A FI 950230 A FI950230 A FI 950230A FI 950230 A FI950230 A FI 950230A
Authority
FI
Finland
Prior art keywords
prodrugs
tumors
treatment
amino acid
nitrogen mustard
Prior art date
Application number
FI950230A
Other languages
Finnish (fi)
Swedish (sv)
Other versions
FI950230A0 (en
FI115048B (en
Inventor
Philip John Burke
Robert Ian Dowell
Anthony Brian Mauger
Caroline Joy Springer
Original Assignee
Zeneca Ltd
Cancer Res Campaign Tech
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB929215636A external-priority patent/GB9215636D0/en
Priority claimed from GB939310884A external-priority patent/GB9310884D0/en
Application filed by Zeneca Ltd, Cancer Res Campaign Tech filed Critical Zeneca Ltd
Publication of FI950230A0 publication Critical patent/FI950230A0/en
Publication of FI950230A publication Critical patent/FI950230A/en
Application granted granted Critical
Publication of FI115048B publication Critical patent/FI115048B/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
    • A61K47/6899—Antibody-Directed Enzyme Prodrug Therapy [ADEPT]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/40—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings
    • C07C271/42—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/54—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/04—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms
    • C07C275/20—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
    • C07C275/24—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C275/40—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by nitrogen atoms not being part of nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/63—Esters of sulfonic acids
    • C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
    • C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
    • C07C309/66—Methanesulfonates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
    • C07C311/51—Y being a hydrogen or a carbon atom

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nanotechnology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Medical Informatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Seasonings (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

Prodrugs, of generic formula I, are disclosed for use in antibody directed enzyme prodrug therapy (ADEPT). The prodrugs are substrates for carboxypeptidase G2 (CPG2) and yield more active cytotoxic drugs than known products of CPG2 catalysed reactions.
FI950230A 1992-07-23 1995-01-19 A process for the preparation of nitrogen mustard derivatives linked to an amino acid FI115048B (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
GB929215636A GB9215636D0 (en) 1992-07-23 1992-07-23 Chemical compounds
GB9215636 1992-07-23
GB939310884A GB9310884D0 (en) 1993-05-26 1993-05-26 Chemical compounds
GB9310884 1993-05-26
GB9301560 1993-07-23
PCT/GB1993/001560 WO1994002450A1 (en) 1992-07-23 1993-07-23 Amino acid linked nitrogen mustard derivatives and their use as prodrugs in the treatment of tumours

Publications (3)

Publication Number Publication Date
FI950230A0 FI950230A0 (en) 1995-01-19
FI950230A true FI950230A (en) 1995-01-19
FI115048B FI115048B (en) 2005-02-28

Family

ID=26301303

Family Applications (1)

Application Number Title Priority Date Filing Date
FI950230A FI115048B (en) 1992-07-23 1995-01-19 A process for the preparation of nitrogen mustard derivatives linked to an amino acid

Country Status (25)

Country Link
US (6) US5405990A (en)
EP (1) EP0651740B1 (en)
JP (1) JP3541037B2 (en)
KR (1) KR100268654B1 (en)
AT (1) ATE172450T1 (en)
AU (1) AU681349B2 (en)
CA (1) CA2101104C (en)
CZ (1) CZ287028B6 (en)
DE (1) DE69321729T2 (en)
DK (1) DK0651740T3 (en)
ES (1) ES2123662T3 (en)
FI (1) FI115048B (en)
GB (1) GB9314960D0 (en)
HK (1) HK1002683A1 (en)
HU (1) HUT69288A (en)
IL (1) IL106459A (en)
MY (1) MY111635A (en)
NZ (1) NZ254864A (en)
PH (1) PH30004A (en)
PL (1) PL174617B1 (en)
RU (1) RU2129542C1 (en)
SK (1) SK281338B6 (en)
TW (1) TW272971B (en)
WO (1) WO1994002450A1 (en)
ZW (1) ZW9293A1 (en)

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US6765019B1 (en) 1999-05-06 2004-07-20 University Of Kentucky Research Foundation Permeable, water soluble, non-irritating prodrugs of chemotherapeutic agents with oxaalkanoic acids
GB0001653D0 (en) * 2000-01-26 2000-03-15 Astrazeneca Uk Ltd Chemical compound
AU2001253479A1 (en) 2000-04-13 2001-10-30 Sts Biopolymers, Inc. Targeted therapeutic agent release devices and methods of making and using the same
US6656718B2 (en) 2000-07-07 2003-12-02 Cancer Research Technology Limited Modified carboxypeptidase enzymes and their use
EP1303481A1 (en) * 2000-07-26 2003-04-23 Patrick Anthony Riley Phenylethylamine derivatives and their use in the treatment of melanoma
GB0102239D0 (en) 2001-01-29 2001-03-14 Cancer Res Ventures Ltd Methods of chemical synthisis
EP1434778A4 (en) * 2001-05-31 2005-07-13 Medarex Inc Cytotoxins, prodrugs, linkers and stabilizers useful therefor
JP2005516011A (en) * 2001-12-13 2005-06-02 ランバクシー ラボラトリーズ リミテッド Crystalline dihydrate cefnidir potassium
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Also Published As

Publication number Publication date
DE69321729D1 (en) 1998-11-26
PH30004A (en) 1996-10-29
IL106459A (en) 1998-02-08
US5958971A (en) 1999-09-28
GB9314960D0 (en) 1993-09-01
HK1002683A1 (en) 1998-09-11
CZ15195A3 (en) 1995-11-15
IL106459A0 (en) 1994-11-11
JP3541037B2 (en) 2004-07-07
HUT69288A (en) 1995-09-28
EP0651740A1 (en) 1995-05-10
ATE172450T1 (en) 1998-11-15
CZ287028B6 (en) 2000-08-16
JPH07509461A (en) 1995-10-19
MY111635A (en) 2000-10-31
FI950230A0 (en) 1995-01-19
FI115048B (en) 2005-02-28
SK281338B6 (en) 2001-02-12
KR100268654B1 (en) 2000-10-16
DK0651740T3 (en) 1999-06-28
CA2101104A1 (en) 1994-01-24
US5714148A (en) 1998-02-03
RU95105246A (en) 1997-04-27
PL307226A1 (en) 1995-05-15
US6277880B1 (en) 2001-08-21
NZ254864A (en) 1996-11-26
SK6995A3 (en) 1995-07-11
HU9500145D0 (en) 1995-03-28
AU681349B2 (en) 1997-08-28
US5587161A (en) 1996-12-24
DE69321729T2 (en) 1999-03-18
EP0651740B1 (en) 1998-10-21
TW272971B (en) 1996-03-21
US5660829A (en) 1997-08-26
WO1994002450A1 (en) 1994-02-03
PL174617B1 (en) 1998-08-31
CA2101104C (en) 2007-01-23
RU2129542C1 (en) 1999-04-27
ZW9293A1 (en) 1994-03-30
US5405990A (en) 1995-04-11
ES2123662T3 (en) 1999-01-16
AU4715693A (en) 1994-02-14

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